Eriksson Mikael, Czene Kamila, Conant Emily F, Hall Per
Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cancers (Basel). 2021 Jan 15;13(2):302. doi: 10.3390/cancers13020302.
Increased breast density decreases mammographic sensitivity due to masking of cancers by dense tissue. Tamoxifen exposure reduces mammographic density and, therefore, should improve screening sensitivity. We modelled how low-dose tamoxifen exposure could be used to increase mammographic sensitivity. Mammographic sensitivity was calculated using the KARMA prospective screening cohort. Two models were fitted to estimate screening sensitivity and detected tumor size based on baseline mammographic density. BI-RADS-dependent sensitivity was estimated. The results of the 2.5 mg tamoxifen arm of the KARISMA trial were used to define expected changes in mammographic density after six months exposure and to predict changes in mammographic screening sensitivity and detected tumor size. Rates of interval cancers and detection of invasive tumors were estimated for women with mammographic density relative decreases by 10-50%. In all, 517 cancers in premenopausal women were diagnosed in KARMA: 287 (56%) screen-detected and 230 (44%) interval cancers. Screening sensitivities prior to tamoxifen, were 76%, 69%, 53%, and 46% for BI-RADS density categories A, B, C, and D, respectively. After exposure to tamoxifen, modelled screening sensitivities were estimated to increase by 0% ( = 0.35), 2% ( < 0.01), 5% ( < 0.01), and 5% ( < 0.01), respectively. An estimated relative density decrease by ≥20% resulted in an estimated reduction of interval cancers by 24% ( < 0.01) and reduction in tumors >20 mm at detection by 4% ( < 0.01). Low-dose tamoxifen has the potential to increase mammographic screening sensitivity and thereby reduce the proportion of interval cancers and larger screen-detected cancers.
乳腺密度增加会因致密组织掩盖癌症而降低乳腺钼靶检查的敏感性。服用他莫昔芬可降低乳腺钼靶密度，因此应能提高筛查敏感性。我们建立模型，探讨如何使用低剂量他莫昔芬来提高乳腺钼靶检查的敏感性。使用KARMA前瞻性筛查队列计算乳腺钼靶检查的敏感性。拟合了两个模型，以根据基线乳腺钼靶密度估计筛查敏感性和检测到的肿瘤大小。估计了BI-RADS分级相关的敏感性。KARISMA试验中2.5mg他莫昔芬组的结果用于确定6个月暴露后乳腺钼靶密度的预期变化，并预测乳腺钼靶筛查敏感性和检测到的肿瘤大小的变化。估计了乳腺钼靶密度相对降低10%-50%的女性的间期癌发生率和浸润性肿瘤的检出率。KARMA研究共诊断出517例绝经前女性癌症：287例（56%）为筛查发现，230例（44%）为间期癌。在服用他莫昔芬之前，BI-RADS密度分类为A、B、C和D的筛查敏感性分别为76%、69%、53%和46%。服用他莫昔芬后，模型估计的筛查敏感性分别提高0%（=0.35）、2%（<0.01）、5%（<0.01）和5%（<0.01）。估计相对密度降低≥20%可使间期癌估计减少24%（<0.01），检测时肿瘤>20mm的减少4%（<0.01）。低剂量他莫昔芬有可能提高乳腺钼靶筛查的敏感性，从而减少间期癌和筛查发现的较大癌症的比例。
